Understanding the developmental processes by which organisms acquire their final body size is a fundamental biological question. Whereas studies of model organisms such as Drosophila have established general paradigms regarding the control of body growth, virtually nothing is known about the mechanisms that regulate the variation in organ and tissue size that is so prevalent in nature. The research proposed here will help to fill in the gaps that exist by using the insect hind (T3) leg as a model system for studying mechanisms that control variation in appendage growth in nature. This system offers several unique advantages. First, the key feature of the evolution of insect hind legs is their differential size increase as compared to their foreleg counterparts. Our strong preliminary data suggest that much of the observed allometric growth of T3 legs results from temporal and spatial variation in the expression of the homeotic gene Ultrabithorax (Ubx). Second, the diversity of T3 legs is extraordinary, encompassing morphologies that vary from slightly to greatly modified. Third, this diversity can be analyzed simultaneously across a wide range of taxonomic levels, from different orders to closely related species. The combination of extreme phenotypic variation in the size of T3 legs and identification of a candidate regulatory locus offers an unparalleled opportunity to study the genetic and developmental variation underlying a key morphological feature in nature. We now propose to examine cellular aspects of differential leg growth (cell size, cell number, apoptosis) and relate them to the differential Ubx expression. We will also analyze a much broader range of insect species as well as functionally test the significance of the observed changes in the Ubx expression. This research will contribute to our understanding of the actual molecular processes underlying variation in organ and tissue growth.